Reductions in police-reported injuries associated with Michigan's safety belt law

This research measured the effects of Michigan's compulsory safety belt use law on traffic crashes and injuries of various severities. Using time-series methods, the authors analyzed monthly frequencies of crash-induced injuries and fatalities from January 1978 through December 1987. Exposure to risk of occupant injury was controlled statistically by including aggregate frequency of crashes as a covariate in time-series models. Effects of economic conditions on traffic crashes were controlled by including an index of unemployment as a covariate. The following statistically significant effects were associated with the safety belt law: (a) In crashes with minor vehicle damage, there was a 14.6% reduction in B-level injuries, an 11.0% reduction in C-level injuries, and a 13.0% reduction in aggregate (KABC) injuries; (b) in crashes with moderate vehicle damage, there was a 16.8% reduction in A-level injuries, an 11.6% reduction in B-level injuries, a 10.7% reduction in C-level injuries, and a 3.6% reduction in aggregate (KABC) injuries; (c) in crashes with severe vehicle damage, there was a 6.3% reduction in fatalities, an 11.8% reduction in B-level injuries, a 4.7% reduction in c-level injuries, and a 5.8% reduction in aggregate (KABC) injuries; (d) for all vehicle damage severities, there was a 14.0% reduction in B-level injuries, an 8.3% reduction in C-level injuries, and a 6.4% reduction in injuries to front-seat occupants. Based on these results, Michigan's adult safety belt law has prevented 31,710 injuries from July 1985 through December 1988.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28625/1/0000439.pd

Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures

Autosomal recessive COX4I1 deficiency has been previously reported in a single individual with a homozygous pathogenic variant in COX4I1, who presented with short stature, poor weight gain, dysmorphic features, and features of Fanconi anemia. COX4I1 encodes subunit 4, isoform 1 of cytochrome c oxidase. Cytochrome c oxidase is a respiratory chain enzyme that plays an important role in mitochondrial electron transport and reduces molecular oxygen to water leading to the formation of ATP. Defective production of cytochrome c oxidase leads to a variable phenotypic spectrum ranging from isolated myopathy to Leigh syndrome. Here, we describe two siblings, born to consanguineous parents, who presented with encephalopathy, developmental regression, hypotonia, pathognomonic brain imaging findings resembling Leigh‐syndrome, and a novel homozygous variant on COX4I1, expanding the known clinical phenotype associated with pathogenic variants in COX4I1

GNA11 brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis

Objective: To describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV). / Methods: A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized. / Results: The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys) was detected in his skin tissue but not in blood (previously published). He underwent an urgent left posterior quadrantectomy for his life-threatening seizures. Histopathology of resected brain tissue showed an increase in leptomeningeal melanocytes and abnormal vasculature, and the exact pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys), previously isolated from his skin tissue but not blood, was detected in his resected brain tissue. / Conclusions: The finding of this variant in affected skin and brain tissue of our patient with PPV supports a unifying genetic diagnosis of his neurocutaneous features

Aberrant function of the C-terminal tail of HIST1H1E Aacelerates cellular senescence and causes premature aging

Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging

De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder

Genetics of disease, diagnosis and treatmen

An Ontological Approach to Inform HMI Designs for Minimizing Driver Distractions with ADAS

ADAS (Advanced Driver Assistance Systems) are in-vehicle systems designed to enhance driving safety and efficiency as well as comfort for drivers in the driving process. Recent studies have noticed that when Human Machine Interface (HMI) is not designed properly, an ADAS can cause distraction which would affect its usage and even lead to safety issues. Current understanding of these issues is limited to the context-dependent nature of such systems. This paper reports the development of a holistic conceptualisation of how drivers interact with ADAS and how such interaction could lead to potential distraction. This is done taking an ontological approach to contextualise the potential distraction, driving tasks and user interactions centred on the use of ADAS. Example scenarios are also given to demonstrate how the developed ontology can be used to deduce rules for identifying distraction from ADAS and informing future designs

Effects of the 65 mph speed limit on injury morbidity and mortality

Effective December 1987 and January 1988, the maximum speed limit on rural limited access highways in Michigan was raised from 55 mph to 65 mph. This study examined the effects of the raised limit on injury morbidity and mortality. A multiple time-series design was used, comparing roads where the speed limit was raised with roads where the limit remained unchanged. Data were collected on numbers and rates of automobile crashes, injuries, and deaths from January 1978 through December 1988. Time-series intervention analyses were conducted to estimate effects associated with the speed limit change while controlling for long-term trends, seasonal cycles, and other patterns. Statistical controls were also included for major factors known to influence crash and injury rates. Results revealed significant increases in casualties on roads where the speed limit was raised, including a 19.2% increase in fatalities, a 39.8% increase in serious injuries, and a 25.4% increase in moderate injuries. Fatalities also increased on 55 mph limited access freeways, suggesting that the 65 mph limit may have spillover effects on segments of freeways where the limit was not changed. No significant changes in fatalities or injuries were found on other types of roads. The increased convenience of reduced travel time with the higher speed limit is obtained at a significant cost in terms of injury morbidity and mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28294/1/0000048.pd